Search

Background: The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome of disease-invaded lesions and non-invaded lung tissue from NTM-PD patients., Methods: We analyzed lung tissues from 23 NTM-PD patients who underwent surgical lung resection. Lung tissues were collected in pairs from each patient, with one sample from a disease-involved site and the other from a non-involved site. Lung tissue microbiome libraries were constructed using 16S rRNA gene sequences (V3-V4 regions)., Results: Sixteen (70%) patients had Mycobacterium avium complex (MAC)-PD, and the remaining seven (30%) had Mycobacterium abscessus-PD. Compared to non-involved sites, involved sites showed greater species richness (ACE, Chao1, and Jackknife analyses, all p = 0.001); greater diversity on the Shannon index (p = 0.007); and genus-level differences (Jensen-Shannon, PERMANOVA p = 0.001). Analysis of taxonomic biomarkers using linear discriminant analysis (LDA) effect sizes (LEfSe) demonstrated that several genera, including Limnohabitans, Rahnella, Lachnospira, Flavobacterium, Megamonas, Gaiella, Subdoligranulum, Rheinheimera, Dorea, Collinsella, and Phascolarctobacterium, had significantly greater abundance in involved sites (LDA >3.00, p <0.05, and q <0.05). In contrast, Acinetobacter had significantly greater abundance at non-involved sites (LDA = 4.27, p<0.001, and q = 0.002). Several genera were differentially distributed between lung tissues from MAC-PD (n = 16) and M. abscessus-PD (n = 7), and between nodular bronchiectatic form (n = 12) and fibrocavitary form (n = 11) patients. However, there was no genus with a significant q-value., Conclusions: We identified differential microbial distributions between disease-invaded and normal lung tissues from NTM-PD patients, and microbial diversity was significantly higher in disease-invaded tissues., Trial Registration: Clinical Trial registration number: NCT00970801., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Interstitial lung abnormalities (ILAs) are associated with the risk of lung cancer and its mortality. However, the impact of ILA on treatment-related complications and survival in patients who underwent curative surgery is still unknown., Research Question: This study aimed to evaluate the significance of the presence of computed tomography-diagnosed ILA and histopathologically matched interstitial abnormalities on postoperative pulmonary complications (PPCs) and the long-term survival of patients who underwent surgical treatment for lung cancer., Study Design and Methods: A matched case-control study was designed to compare PPCs and mortality among 50 patients with ILA, 50 patients with idiopathic pulmonary fibrosis (IPF) and 200 controls. Cases and controls were matched by sex, age, smoking history, tumour location, the extent of surgery, tumour histology and pathological TNM stage., Results: Compared with the control group, the OR of the prevalence of PPCs increased to 9.56 (95% CI 2.85 to 32.1, p<0.001) in the ILA group and 56.50 (95% CI 17.92 to 178.1, p<0.001) in the IPF group. The 5-year overall survival (OS) rates of the control, ILA and IPF groups were 76% (95% CI 71% to 83%), 52% (95% CI 37% to 74%) and 32% (95% CI 19% to 53%), respectively (log-rank p<0.001). Patients with ILA had better 5-year OS than those with IPF (log-rank p=0.046) but had worse 5-year OS than those in the control group (log-rank p=0.002)., Conclusions: The presence of radiological and pathological features of ILA in patients with lung cancer undergoing curative surgery was associated with frequent complications and decreased survival., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Limited data are available regarding the impact of the antibiotic maintenance period on the redevelopment of nontuberculous mycobacteria-pulmonary disease (NTM-PD) after microbiological cure of Mycobacterium avium complex (MAC)-PD. This retrospective study included 631 MAC-PD patients who achieved microbiological cure between 1994 and 2021. Data on the antibiotic maintenance period, defined as the time between culture conversion and treatment completion, were collected. Redevelopment, the subsequent diagnosis of NTM-PD regardless of causative organism after microbiological cure, was investigated. Factors associated with redevelopment were analyzed after adjusting for disease severity using the b ody mass index, a ge, c avity, e rythrocyte sedimentation rate, and s ex (BACES) scoring system. In total, 205 (33%) patients experienced redevelopment, with a median maintenance period after culture conversion of 15.0 months (interquartile range, 13.0 to 22.0 months). A greater proportion of patients with the nodular bronchiectatic form of MAC-PD (87% versus 80%, P  = 0.033) and a longer maintenance period (median 15.0 versus 14.0 months, P  < 0.001) were noted in the redevelopment group compared with the nonredevelopment group. The cumulative rate of redevelopment according to the maintenance period did not differ between the >12-month and ≤12-month groups in the total patient population or the subgroups sorted according to BACES severity. No association between a maintenance period >12 months and redevelopment was identified in multivariate models. Extending the antibiotic maintenance period more than 12 months did not reduce the redevelopment rate even with adjustment for disease severity, suggesting the need to further optimize the duration of the antibiotic maintenance period. IMPORTANCE Limited data are available regarding the impact of the antibiotic maintenance period on the redevelopment of Mycobacterium avium complex-pulmonary (MAC-PD) disease after microbiological cure. To improve treatment outcomes and reduce the recurrence rate, current guidelines recommend maintenance of antibiotics for a minimum of 12 months after achievement of negative culture conversion. However, the optimal duration of antibiotic therapy for MAC-PD is not currently known. Moreover, in real-world clinical practice, total antibiotic duration is mainly impacted by the length of the maintenance period; however, it is unknown whether extending the maintenance period is beneficial for preventing redevelopment of NTM-PD. Our study may help to address concerns regarding the antibiotic maintenance period after achievement of negative culture conversion in patients with MAC-PD.

The aim of our study was to investigate the incidence of and risk factors for coronavirus disease 2019 (COVID-19) in patients with non-tuberculous mycobacterial-pulmonary disease (NTM-PD). A total of 3,866 patients with NTM-PD were retrospectively identified from a single center. Compared to the general population of Korea, patients with NTM-PD had a substantially increased age-standardized incidence of COVID-19 from January 2020 to February 2021 (2.1% vs. 0.2%). The odds of being infected with COVID-19 was particularly higher in patients who received treatment for NTM-PD than in those who did not receive treatment for NTM-PD (adjusted odd ratio = 1.99, 95% confidence interval = 1.09-3.64, P = 0.026). Patients with NTM-PD might be regarded as a high-risk group for COVID-19 and may need a more proactive preventive strategy for COVID-19 and other pandemics in the future., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: Limited data are available regarding when to start treatment after a diagnosis of nontuberculous mycobacteria-pulmonary disease (NTM-PD) or regarding how achieving culture conversion affects NTM-PD outcomes., Research Question: Does the time between diagnosis and antibiotic initiation influence culture conversion or all-cause mortality in NTM-PD, and is there any association between achieving culture conversion after antibiotics and reduced all-cause mortality?, Study Design and Methods: We evaluated 712 patients who received antibiotics for 6 or more months after diagnosis of NTM-PD between July 1997 and December 2013. Data on the waiting period, defined as the interval between diagnosis and treatment initiation, and on outcomes such as culture conversion by 6 months or death were collected. Factors associated with outcomes were analyzed after adjusting for disease severity, using the BMI, age, cavity, erythrocyte sedimentation rate (ESR), and sex (BACES) system., Results: Thirty-eight percent of study patients had mild disease, 48% had moderate disease, and 14% had severe disease. The median waiting period without antibiotics among all patients was 4.8 (interquartile range, 1.3-20.8) months. After treatment initiation, 479 (67%) patients achieved culture conversion within 6 months, and 135 (19%) patients died. In univariable and multivariable models adjusted for BACES severity, no association between the waiting period and 6-month culture conversion or death was identified. However, 6-month culture conversion demonstrated a significant negative correlation with death (crude hazard ratio [HR], 0.46, 95% CI, 0.33-0.65; adjusted HR, 0.51, 95% CI, 0.35-0.74). In the subgroup treated for more than 12 months, 12-month culture conversion was also associated with reduced death (adjusted HR, 0.51; 95% CI, 0.33-0.78)., Interpretation: It may be reasonable to start antibiotics according to the "watchful waiting" strategy for NTM-PD, but given the survival benefits, achieving culture conversion is an important goal for patients in need of treatment., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Mycobacterium avium complex pulmonary disease (MAC-PD) requires long-term treatment. We analyzed the outcomes of 992 MAC-PD patients according to disease severity and compared the outcomes of intermittent and daily therapy for mild disease. Patients were divided into groups according to severity using the body mass index, age, cavity, erythrocyte sedimentation rate, and sex (BACES) system, and culture conversion rates were evaluated. We also evaluated the effects of intermittent treatment on the culture conversion rates in mild disease group. Using the BACES, 992 patients were divided into mild (n = 331), moderate (n = 503), and severe (n = 158) disease groups, and culture conversion at the end of treatment was achieved in 85% (282/331), 80% (403/503), and 61% (97/158), respectively. Differences in culture conversion among the severity groups were significant (p < 0.001). In patients with mild disease, culture conversion rates were similar between intermittent (84%, 166/198) and daily (87%, 116/133) treatment (p = 0.396), and intermittent antibiotic therapy did not negatively impact culture conversion (adjusted hazard ratio 1.08; confidence interval 0.83-1.41; p = 0.578). MAC-PD patients with mild disease had higher culture conversion rates. Daily and intermittent therapy yielded similar culture conversion rates for mild disease. Treatment strategies with lower pill burden may be applicable in mild MAC-PD., (© 2022. The Author(s).)

Background: Mycobacterium abscessus pulmonary disease (M abscessus-PD) is challenging to treat because of its resistance to antibiotics., Research Question: What are the outcomes of treatment-naive patients with M abscessus-PD treated with inhaled amikacin-containing multidrug regimens?, Study Design and Methods: We identified 82 treatment-naive patients with M abscessus-PD from a prospective observational cohort treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received IV amikacin, imipenem (or cefoxitin), and oral azithromycin. Oral clofazimine was added in cases of (1) M abscessus subspecies abscessus (here M abscessus) or (2) M abscessus subspecies massiliense (here M massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from an injectional to inhalational form., Results: Of 82 patients, 46 (56%) had M massiliense-PD and 36 (44%) had M abscessus-PD. Among 59 patients with nodular bronchiectatic disease (72%), 23 of 59 had a concurrent cavitary lesion. The remaining 23 patients (28%) had fibrocavitary disease. Twelve months after treatment initiation, cure was achieved in 53 patients (65%): 42 of 46 patients (91%) with M massiliense-PD and 11 of 36 patients (31%) with M abscessus-PD (P < .001). Symptomatic and radiologic improvements were observed in 72 patients (88%) and 64 patients (78%), respectively, with significantly greater improvement in patients with M massiliense-PD (symptom improvement, 96% vs 78% [P = .047]; improvement on CT scanning, 93% vs 61% [P = .002])., Interpretation: Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M massiliense-PD. However, more effective treatments are needed for M abscessus-PD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Pulmonary disease (PD) due to nontuberculous mycobacteria (NTM) is increasing globally, but specific biomarkers for NTM-PD have not been established. As circulating miRNAs are promising biomarkers for various diseases, we investigated whether miRNAs have potential as NTM-PD biomarkers. Sera from 12 NTM-PD patients due to Mycobacterium avium, M. intracellulare, M. abscessus, or M. massiliense and three healthy controls were initially evaluated via small RNA sequencing. Multiple miRNAs showed significant differences in expression in patients compared to in healthy controls, with some expression differences unique to PD caused by a specific mycobacterial species. Notably, 14 miRNAs exhibited significant expression differences in PD associated with all four mycobacteria. Validation by quantitative reverse-transcription-PCR in an additional 40 patients with NTM-PD and 40 healthy controls confirmed that four differentially expressed miRNAs (hsa-miR-484, hsa-miR-584-5p, hsa-miR-625-3p, and hsa-miR-4732-5p) showed significantly higher serum expressions in NTM-PD patients than in controls. Receiver operating characteristic curve analysis of these four miRNAs supported the discriminative potential for NTM-PD and their combination provided an improved diagnostic value for NTM-PD. Furthermore, bioinformatics analysis revealed their 125 target genes, which were mostly associated with immune responses. Collectively, this study identified four miRNAs as potential biomarkers for NTM-PD and provided insight into NTM-PD pathophysiology.

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form.A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows: Mycobacterium avium (n=655), M. intracellulare (n=487), M. abscessus (n=129) and M. massiliense (n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data.The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality: M. intracellulare had an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03-1.91; M. abscessus had an aHR of 2.19, 95% CI 1.36-3.51; and M. massiliense had an aHR of 0.99, 95% CI 0.61-1.64, compared to M. avium Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12-2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57-3.08), compared to the non-cavitary nodular bronchiectatic form.Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics., Competing Interests: Conflict of interest: B.W. Jhun has nothing to disclose. Conflict of interest: S.M. Moon has nothing to disclose. Conflict of interest: K. Jeon has nothing to disclose. Conflict of interest: O.J. Kwon has nothing to disclose. Conflict of interest: H. Yoo has nothing to disclose. Conflict of interest: K.C. Carriere has nothing to disclose. Conflict of interest: H.J. Huh has nothing to disclose. Conflict of interest: N.Y. Lee has nothing to disclose. Conflict of interest: S.J. Shin has nothing to disclose. Conflict of interest: C.L. Daley reports grants from Insmed Inc., and has served on advisory boards for Insmed, Johnson & Johnson, Spero and Horizon, outside the submitted work. Conflict of interest: W-J. Koh reports personal fees for consultancy from Insmed, outside the submitted work., (Copyright ©ERS 2020.)

Lung Transplant recipients are at increased risk of complicated diverticular disease. We aim to assess the rate of diverticular surgery in a postlung transplantation population and identify risk factors for surgery. We performed a retrospective cohort study of lung transplant recipients from 2007 to 2011. Demographic variables were evaluated with the Mann-Whitney U and chi-squared tests. Cox regression was performed to evaluate 1- and 2-year landmark survival, assess predictor variables of diverticular surgery and evaluate impact of surgery on CLAD development. Of 17 of 158 patients (10.7%) underwent diverticular-related surgery. Surgical patients had significantly worse survival than nonsurgical patients at 1 year [aHR 2.93 (1.05-8.21), P = 0.041] and 2 year [aHR 4.17 (1.26-13.84), P = 0.020] landmark analyses. Transplant indication of alpha-1 antitrypsin disease and cystic fibrosis were significantly associated with the need for diverticular surgery. Emergent surgery was associated with poorer survival [aHR 5.12(1.00-26.27), P = 0.050]. Lung transplant patients requiring surgery for complicated diverticular disease have significantly poorer survival than those who do not require surgery. Surgery was more common in patients transplanted for A1AT and CF. Optimal assessment and risk stratification of diverticular disease is necessary to prevent excessive morbidity and mortality following transplantation., (© 2019 Steunstichting ESOT.)

Background: Information about the natural history of nontuberculous mycobacterial pulmonary disease (NTM-PD) is limited. The purpose of this study was to evaluate the long-term natural history of non-cavitary nodular bronchiectatic NTM-PD and the factors associated with treatment initiation and the frequency of spontaneous sputum culture conversion after diagnosis of NTM-PD., Methods: We evaluated 1,021 patients with newly diagnosed non-cavitary nodular bronchiectatic NTM-PD caused by Mycobacterium avium complex or M. abscessus between 2003 and 2013., Results: Of 1,021 patients, 562 (55%) initiated antibiotic treatment and 459 (45%) did not. Young age (adjusted hazard ratio [aHR] = 0.99; 95% confidence interval [CI] = 0.98-0.99), low body mass index (aHR = 0.96; 95% CI = 0.93-0.99), previous history of tuberculosis (aHR = 1.23; 95% CI = 1.01-1.50), respiratory complaints such as cough (aHR = 1.36; 95% CI = 1.05-1.75) and sputum production (aHR = 1.47; 95% CI = 1.13-1.91), and high number of involved lobes on high-resolution computed tomography (aHR = 1.22; 95% CI = 1.14-1.31) were associated with treatment initiation. Of 459 patients who did not initiate treatment, 157 (34%) showed spontaneous sputum culture conversion. None of the clinical factors was associated with spontaneous conversion. After spontaneous culture conversion, 26 of 157 (17%) showed redeveloped NTM-PD caused by a species different from the original species., Conclusions: The natural history of non-cavitary nodular bronchiectatic NTM-PD is variable. After diagnosis, the decision to initiate antibiotic therapy should be individualized based on consideration of the risk factors for disease progression. However, for patients who do not start antibiotic therapy, continuous and lifetime follow-up is recommended to manage underlying bronchiectasis and the possibility of late progression of NTM-PD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Mycobacterium kansasii is a major pathogen associated with nontuberculous mycobacterial pulmonary disease. For treatment of M. kansasii pulmonary disease, daily therapy with isoniazid, rifampin, and ethambutol is traditionally recommended. Although a regimen containing a macrolide, instead of isoniazid, has been recently recommended, supporting data are limited. We compared the treatment outcomes of a macrolide-containing regimen (macrolide group) and an isoniazid-containing regimen (isoniazid group) on patients with M. kansasii pulmonary disease., Methods: A total of 49 patients were identified between January 2002 and December 2016. Treatment outcomes for the isoniazid group (n = 24) and the macrolide group (n = 25) were compared., Results: Baseline characteristics of the isoniazid and macrolide groups were similar. Favorable outcomes did not differ between the isoniazid group (79%, n = 19) and macrolide group (88%, n = 22, P = 0.463). Total treatment duration (median 17.9 months vs. 15.4 months; P = 0.712) and time to culture conversion (median 2.0 months vs. 1.2 months; P = 0.838) were also similar between the isoniazid and macrolide groups. Five patients who completed three-times-weekly intermittent treatment containing a macrolide for non-cavitary M. kansasii pulmonary disease achieved negative sputum culture conversion within 12 months of treatment. Only one patient experienced recurrence of M. kansasii pulmonary disease in the isoniazid group., Conclusions: A macrolide-containing regimen appears to be as effective as an isoniazid-containing regimen for treatment of M. kansasii pulmonary disease. Additionally, intermittent therapy containing a macrolide could be an alternative treatment option for non-cavitary M. kansasii pulmonary disease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rationale: Patients with refractory Mycobacterium avium complex lung disease (MAC-LD) undergo long-term macrolide therapy, but macrolide resistance develops infrequently., Objectives: The aim of this study was to determine whether reinfection was a factor in the low incidence of macrolide resistance in patients with refractory MAC-LD., Methods: Among 481 patients with treatment-naive MAC-LD who started antibiotic treatment between January 2002 and December 2013, we identified 72 patients with refractory disease, characterized by persistently positive sputum cultures despite ≥12 months of treatment. Molecular analyses of the 23S ribosomal RNA gene responsible for macrolide resistance and serial mycobacterial genotyping were performed using stored MAC isolates., Measurements and Main Results: The median duration of treatment was 32 months (interquartile range, 24-41 mo) in 72 patients. After treatment for a median of 33 months (interquartile range, 21-44 mo), macrolide resistance developed in 16 (22%) patients. Molecular analysis of isolates from 15 patients revealed that 80% (12 of 15) had a point mutation at position 2,058 or 2,059 of the 23S ribosomal RNA gene. Of the 49 patients who had stored pre- and post-treatment isolates, mycobacterial genotyping revealed that reinfection by new MAC strains occurred in 36 (73%) patients. New MAC strains were found in 24 (49%) patients, and mixed infections with original and new strains occurred in 12 (24%) patients. Only 13 (27%) patients had persistent infections with their original MAC strains., Conclusions: Refractory MAC-LD is commonly caused by reinfection with new strains rather than persistence of the original strain, which may explain the infrequent development of macrolide resistance in refractory MAC-LD. Clinical trial registered with www.clinicaltrials.gov (NCT00970801).

In 2005, the Lung Allocation Score (LAS) was implemented as the allocation system for lungs in the US. We sought to compare 5-year lung transplant outcomes before and after the institution of the LAS. Between 2000 and 2011, 501 adult patients were identified, with 132 from January 2000 to April 2005 (Pre-LAS era) and 369 from May 2005 to December 2011 (Post-LAS era). Kruskal-Wallis or chi-squared test was used to determine significance between groups. Survival was censored at 5 years. Overall, the post-LAS era was associated with more restrictive lung disease, higher LAS scores, shorter wait-list times, more preoperative immunosuppression, and more single lung transplantation. In addition, post-LAS patients had higher O 2 requirements with greater preoperative pulmonary impairment. Postoperatively, 30-day mortality improved in post-LAS era (1.6% vs 5.3%, P = .048). During the pre- and post-LAS eras, 5-year survival was 52.3% and 55.3%, respectively (P = .414). The adjusted risk of mortality was not different in the post-LAS era (P = .139). Freedom from chronic lung allograft dysfunction was significantly higher in the post-LAS era (P = .002). In this single-center report, implementation of the LAS score has led to allocation to sicker patients without decrement in short- or medium-term outcomes. Freedom from CLAD at 5 years is improving after LAS implementation., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Intermittent, three-times-weekly oral antibiotic therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic (NB) Mycobacterium avium complex (MAC) lung disease. However, intermittent therapy is not recommended for patients who have been previously treated. We evaluated 53 patients with recurrent noncavitary NB MAC lung disease who underwent antibiotic treatment for ≥12 months with daily therapy ( n = 26) or intermittent therapy ( n = 27) between January 2008 and December 2015. Baseline characteristics were comparable between daily therapy and intermittent therapy groups. Sputum culture conversion rates did not differ between daily therapy (21/26, 81%) and intermittent therapy (22/27, 82%) groups. Compared to the etiologic organism at the time of previous treatment, recurrent MAC lung disease was caused by the same MAC species in 38 patients (72%) and by a different MAC species in 15 patients (28%). Genotype analysis in patients with sequenced paired isolates revealed that 86% (12/14) of cases with same species recurrence were due to reinfection with a new MAC genotype. In conclusion, most recurrent noncavitary NB MAC lung disease cases were caused by reinfection rather than relapse. Intermittent antibiotic therapy is a reasonable treatment strategy for recurrent noncavitary NB MAC lung disease., (Copyright © 2018 American Society for Microbiology.)

The effect of the clinical phenotype of Mycobacterium avium complex (MAC) lung disease on treatment outcome and redevelopment of nontuberculous mycobacterial (NTM) lung disease after treatment completion has not been studied systematically.We evaluated 481 treatment-naïve patients with MAC lung disease who underwent antibiotic treatment for ≥12 months between January 2002 and December 2013.Out of 481 patients, 278 (58%) had noncavitary nodular bronchiectatic (NB) disease, 80 (17%) had cavitary NB disease and 123 (25%) had fibrocavitary disease. Favourable outcome was higher in patients with noncavitary disease (88%) than in patients with cavitary disease (76% for fibrocavitary and 78% for cavitary NB disease; p<0.05). Cavitary disease was independently associated with unfavourable outcomes (p<0.05). Out of 402 patients with favourable outcomes, 118 (29%) experienced redevelopment of NTM lung disease, with the same MAC species recurring in 65 (55%) patients. The NB form was an independent risk factor for redevelopment of NTM lung disease (p<0.05). In patients with recurrent MAC lung disease due to the same species, bacterial genotyping revealed that 74% of cases were attributable to reinfection and 26% to relapse.Treatment outcomes and redevelopment of NTM lung disease after treatment completion differed by clinical phenotype of MAC lung disease., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Mycobacterium avium complex (MAC) was originally composed of 2 species, M. avium and M. intracellulare. However, several new species closely related to M. intracellulare have recently been identified. In addition, M. avium has been further subdivided into 4 subspecies. The aim of this study was to determine the proportion of different MAC species recovered from respiratory specimens and to elucidate the clinical relevance of these species. Clinical isolates, from 219 patients, that had been initially identified as M. avium or M. intracellulare by non-sequencing methods were reidentified using multilocus sequence typing, and the clinical significance of the identified species was then investigated. Of 91 isolates originally identified as M. intracellulare, 75 (82%) were confirmed to be M. intracellulare, 8 (9%) isolates were identified as M. chimaera, and 4 (4%) isolates each were identified as "M. indicus pranii" and M. yongonense. The 128 isolates originally designated as M. avium were determined to be M. avium subsp. hominissuis. Of the 219 patients, 146 (67%) met the diagnostic criteria for MAC lung disease, and for each MAC species, the proportion of patients meeting these criteria was as follows: M. intracellulare (54/75, 72%), M. chimaera (3/8, 38%), "M. indicus pranii" (3/4, 75%), M. yongonense (2/4, 50%), and M. avium subsp. hominissuis (84/128, 66%). In summary, multilocus sequence typing of respiratory isolates initially identified as MAC revealed that, although most isolates were M. avium subsp. hominissuis or M. intracellulare, approximately 7% were newer MAC members, with clinical evidence supporting their potential pathogenicity for humans., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Treatment outcomes of patients with Mycobacterium abscessus subspecies abscessus lung disease are poor, and the microbial characteristics associated with treatment outcomes have not been studied systematically. The purpose of this study was to identify associations between microbial characteristics and treatment outcomes in patients with M. abscessus lung disease., Methods: Sixty-seven consecutive patients with M. abscessus lung disease undergoing antibiotic treatment for ≥12 months between January 2002 and December 2012 were included. Morphotypic and genetic analyses were performed on isolates from 44 patients., Results: Final sputum conversion to culture negative occurred in 34 (51%) patients. Compared to isolates from 24 patients with persistently positive cultures, pretreatment isolates from 20 patients with final negative conversion were more likely to exhibit smooth colonies (9/20, 45% vs 2/24, 8%; P = .020), susceptibility to clarithromycin (7/20, 35% vs 1/24, 4%; P = .015), and be of the C28 sequevar with regard to the erm(41) gene (6/20, 30% vs 1/24, 4%; P = .035). Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Genotypic analysis revealed that most episodes (22/24, 92%) of persistently positive cultures during antibiotic treatment and all cases of microbiologic recurrence after treatment completion were caused by different M. abscessus genotypes within a patient., Conclusions: Precise identification to the subspecies level and analysis of mycobacterial characteristics could help predict treatment outcomes in patients with M. abscessus lung disease. Treatment failures and recurrences are frequently associated with multiple genotypes, suggesting reinfection., Clinical Trials Registration: NCT00970801., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Objective: Increasing numbers of lung transplant candidates have cardiac conditions that affect their survival after transplantation. Our objective was to determine if patients who undergo concomitant cardiac surgery (CCS) during the lung transplant procedure have similar outcomes, as a cohort of isolated lung transplant recipients., Methods: This was a retrospective, observational, matched-cohort analysis. The records of lung transplant recipients who underwent CCS from August 2000 to August 2013 were reviewed. A cohort of isolated lung transplant recipients, matched on the basis of age, lung allocation score, diagnosis, type of procedure, and era, was identified. The primary endpoint of this trial was 5-year survival. The secondary endpoints were primary graft dysfunction, grade III, at 72 hours, intensive care unit and hospital length of stay, and 5-year major adverse cardiac event rates., Results: A total of 120 patients underwent lung transplantation and CCS. Compared with the isolated lung transplant group, the donor, recipient, and operation characteristics were similar. No difference was found in the survival of the 2 groups for up to 5 years, or in the incidence of primary graft dysfunction Grade III at 72 hours, intensive care unit length of stay, invasive ventilation, hospital length of stay, or incidence of 5-year major adverse cardiac events., Conclusions: Lung transplant recipients undergoing CCS have early and midterm clinical outcomes similar to those of isolated lung transplant recipients. Given that this report is the largest published experience, offering cardiac surgery at the time of lung transplantation, to selected patients, remains justified., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Patient- and procedure-related factors associated with postoperative pulmonary complications (PPCs) have changed over the last decade. Therefore, we sought to identify independent risk factors of PPCs and to develop a clinically applicable scoring system. We retrospectively analyzed clinical data from 2,059 patients who received preoperative evaluations from respiratory physicians between June 2011 and October 2012. A new scoring system for estimating PPCs was developed using beta coefficients of the final multiple regression models. Of the 2,059 patients studied, 140 (6.8%) had PPCs. A multiple logistic regression model revealed seven independent risk factors (with scores in parentheses): age ≥70 years (2 points), current smoker (1 point), the presence of airflow limitation (1 point), American Society of Anesthesiologists class ≥2 (1 point), serum albumin <4 g/dL (1 point), emergency surgery (2 points), and non-laparoscopic abdominal/cardiac/aortic aneurysm repair surgery (4 points). The area under the curve was 0.79 (95% CI, 0.75-0.83) with the newly developed model. The new risk stratification including laparoscopic surgery has a good discriminative ability for estimating PPCs in our study cohort. Further research is needed to validate this new prediction rule.

Little information is available regarding changes in immune status for patients with Mycobacterium avium complex (MAC) lung disease during antibiotic therapy. Serum immunomolecules from 42 patients with MAC lung disease were assayed comparatively using an array-based system according to (i) patients with MAC lung disease at the time of diagnosis versus healthy controls and (ii) alterations after 12 months of antibiotic therapy in the MAC lung disease group. In addition, cytokine analyses were performed to determine whether cytokine responses were associated specifically with the disease phenotype, treatment outcome and aetiological agent. Notably, the serum concentrations of type 1 cytokine-associated molecules, such as CD40L, interferon (IFN)-γ, interleukin (IL)-8 and IL-23, were decreased significantly in patients at the time of diagnosis, suggesting that these molecules may serve as indicators of host susceptibility to MAC disease. Although the overall serum level of T helper type 1 (Th1)-related molecules, such as CD40L and IFN-γ, was restored after treatment, Th17-related cytokines, such as IL-17 and IL-23, were down-regulated significantly at 12 months post-treatment compared to pretreatment. Furthermore, these cytokine patterns differed among patient subgroups. Decreased serum concentrations of IL-17 and/or IL-23 were associated with failure of sputum conversion, the fibrocavitary disease phenotype and M. intracellulare lung disease. Thus, the reciprocal balance between Th1 and Th17 immunity during antibiotic therapy for MAC lung disease is critical for dictating the treatment response. In conclusion, a low level of Th1-related immunomolecules may perpetuate MAC lung disease, and the serum concentrations of Th17-related cytokines can reflect the treatment outcome, disease phenotype and aetiological agent., (© 2013 British Society for Immunology.)

Background: The concept of healthcare-associated pneumonia (HCAP) exists to identify patients infected with highly resistant pathogens who are exposed to the healthcare environment. However, many studies have included immunosuppressed patients who were excluded from the original concept., Objectives: The risk factors of potentially drug-resistant (PDR) pathogens in patients with pneumonia developed outside the hospital were reevaluated after excluding the patients who had immunosuppression., Methods: This was a retrospective study of prospectively collected data from all consecutive patients with pneumonia who were admitted to hospital via the emergency department between January 2008 and December 2011., Results: Pathogens were isolated in a total of 315 patients with pneumonia from our cohort; 33% with PDR pathogens did not meet the criteria for HCAP, but 44% without PDR pathogens did meet the criteria. Variables independently associated with PDR included nursing home residency, hospitalization in the preceding 90 days, antibiotics in the 30 days prior to pneumonia, poor function status and chronic lung disease. The new predictive scoring system based on the logistic regression model had a higher predictive power for the risk of PDR pathogens than the presence of the risk factors or the HCAP criteria., Conclusions: Functional status, pulmonary comorbidity and previous exposure to the healthcare environment were significantly associated with acquiring PDR pathogens in immunocompetent patients with pneumonia that developed out of hospital. However, a risk stratification model was more accurate than the presence of the risk factors or the HCAP criteria for assessing the probability of PDR pathogens.

Background: Although focal ground-glass opacity (GGO) lung nodules are generally reported to grow slowly, their natural course is unclear. The purpose of this study was to elucidate the natural course of screening-detected pure GGO lung nodules in patients with no history of malignancy., Methods: We retrospectively reviewed the database of subjects who had undergone screenings involving low-dose CT scans. We included patients with pure GGO lung nodules who were followed for > 2 years after the initial screening., Results: Between June 1997 and September 2006, 122 pure GGO nodules were found in 89 patients. The median nodule size was 5.5 mm (range, 3-20 mm) in the largest diameter on initial low-dose CT scan. The median follow-up period per patient was 59 months. On a per-person basis, the frequency of growth was 13.5% (12 of 89 patients). On a per-nodule basis, the frequency of growth was 9.8% (12 of 122 nodules). Nodule growth was significantly associated with initial size and new development of an internal solid portion. The median volume doubling time was 769 days for growing pure GGO nodules. A total of 11 growing nodules were surgically validated, and all lesions were confirmed as primary lung cancer., Conclusions: About 90% of the screening-detected pure GGO lung nodules did not grow during long-term follow-up in subjects with no history of malignancy and most growing nodules had an indolent clinical course. A strategy of long-term follow-up and selective surgery for growing nodules should be considered for pure GGO lung nodules.

Purpose: Vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) are major mediators of angiogenesis and are induced by tissue inflammation and hypoxia. The purpose of this study was to investigate whether serum VEGF and Ang-2 are associated with the presence of hemoptysis and the extent of systemic inflammation in patients with inflammatory lung diseases., Materials and Methods: We prospectively enrolled 52 patients with inflammatory lung disease between June 2008 and October 2009., Results: The median values of VEGF and Ang-2 were 436 pg/mL and 2383 pg/mL, respectively. There was a significant positive correlation between serum Ang-2 and VEGF levels. VEGF levels were not significantly different according to the presence of hemoptysis. C-reactive protein (CRP) and Ang-2 level were significantly higher in patients without hemoptysis (n=26) than in those with hemoptysis (n=26; p<0.001 and p<0.001, respectively). CRP and arterial oxygen tension (PaO₂) were significantly correlated with both serum VEGF (p=0.032 and p=0.016, respectively) and Ang-2 levels (p<0.001 and p=0.041, respectively), after adjusting for other factors. Age and the absence of hemoptysis were factors correlated with serum Ang-2 levels., Conclusion: Our study suggests that serum VEGF and Ang-2 levels are associated with PaO₂ and the severity of inflammation rather than the presence of hemoptysis in patients with inflammatory lung diseases. Thus, hemoptysis may not be mediated by increased serum levels of VEGF and Ang-2 in patients with inflammatory lung diseases, and further studies are required to determine the mechanisms of hemoptysis.

Objective and Design: To determine how pulmonary paragonimiasis may be confused with lung cancer, we retrospectively analysed the clinical and radiological characteristics of 47 patients (27 males, median age 55 years; interquartile range 49-61) with serologically or histopathologically confirmed pulmonary paragonimiasis seen between October 2004 and December 2009., Results: Respiratory symptoms were present in 29 (62%) patients; the remaining 18 (38%) were asymptomatic. Chest radiography (CXR) revealed intrapulmonary parenchymal lesions (n = 35, 75%) more frequently than pleural lesions (n = 11, 23%). Of the 47 patients, 28 (60%) were referred for suspected lung cancer. The majority of these patients had no symptoms, and 22 (79%) patients with suspected lung cancer had nodular or mass lesions on CXR. As a result, additional diagnostic procedures were performed to make an accurate diagnosis in these patients, including bronchoscopy in 20, transthoracic lung biopsy in 11 and fluorodeoxyglucose positron emission tomography in seven. Surgical lung resection was performed unnecessarily in six patients., Conclusions: Pulmonary paragonimiasis presenting with nodular or mass lesions on CXR is common. Clinicians should therefore include pulmonary paragonimiasis in the differential diagnosis of asymptomatic nodular lesions in the lung in patients who have lived in or travelled to paragonimiasis-endemic areas.

Purpose: The optimal treatment regimen for Mycobacterium avium complex (MAC) lung disease has not yet been fully established. We evaluated the efficacy of standardized combination antibiotic therapy and the factors that might affect unfavorable microbiologic responses in patients with MAC pulmonary disease., Materials and Methods: This retrospective study reviewed data from 96 patients (56 females; median age 59 years) treated with newly diagnosed MAC lung disease between January 2003 and December 2006., Results: All patients received standardized combination antibiotic therapy, consisting of clarithromycin, rifampicin, and ethambutol. Streptomycin was additionally given in 72 patients (75%) for a median duration of 4.5 months. The overall favorable microbiologic response rate was 79% (76/96); 20 patients (21%) had unfavorable microbiologic responses, including failure to sputum conversion (n = 13), relapse (n = 3), and MAC-related death (n = 4). A positive sputum acid-fast bacillus smear at the start of treatment was an independent predictor of an unfavorable microbiologic response., Conclusion: Standardized combination antibiotic therapy consisting of clarithromycin, rifampicin, and ethambutol with or without initial use of streptomycin is effective in treating patients with newly diagnosed MAC lung disease.

Purpose: While Mycobacterium kansasii is a common cause of nontuberculous mycobacterial (NTM) lung disease in many developed countries, M. kansasii is infrequently isolated in Korea. We investigated the clinical and radiological features and treatment outcomes of M. kansasii lung disease in Korea retrospectively., Materials and Methods: We identified 41 patients with M. kansasii lung disease who met the diagnostic criteria for NTM lung disease in two tertiary referral hospitals in Seoul, Korea, between January 1998 and December 2007., Results: Their median age was 63 years [interquartile range (IQR) 51-75 years] and 33 (81%) were men. Twenty-three patients (56%) were smokers and 13 patients (32%) had previous pulmonary tuberculosis. The most common radiographic findings were nodules (n = 22, 54%) and consolidation (n = 22, 54%). Cavitation was present in 13 patients (32%). Thirty-one patients (76%) were treated with isoniazid, rifampin, and ethambutol. The median treatment duration was 16 months (IQR 9-18 months). The negative conversion rate after 12 months of treatment was 95%., Conclusion: Clinicians should be aware of the various radiographic manifestations of M. kansasii lung disease. With appropriate treatment, these patients have a good prognosis.

Background and Objective: Bronchoscopic resection of endobronchial hamartomas has been reported to have a favourable outcome. This study describes the bronchoscopic features of endobronchial hamartoma and reports the clinical outcome of bronchoscopic intervention., Methods: A retrospective analysis was conducted of patients with histologically proven endobronchial hamartomas, diagnosed in the 10-year period 1999-2009 to elucidate the clinical, radiological and bronchoscopic features of hamartoma and to describe the clinical outcomes., Results: Seventeen of the 135 patients with pulmonary hamartomas were diagnosed as having endobronchial hamartomas. CXR was abnormal in 11 of the 17 patients. On chest CT (n = 16), the median diameter of the lesion was 15.6 mm. Calcification and areas of focal fat in the lesion, the diagnostic CT findings of pulmonary hamartoma, were found in two of 16 (12.5%) patients. At bronchoscopy (n = 16), all tumours had a mass appearance and most were smooth surfaced round masses (50.0%) with 18.8% having a 'stalk'. Bronchoscopic forceps biopsies were performed in 13 patients, which resulted in five patients (38.5%) being diagnosed with endobronchial hamartoma. Fifteen patients were treated with rigid or flexible bronchoscopic resection, one had lobectomy, and one had no intervention. No procedure-related mortalities or late complications developed., Conclusions: Bronchoscopic intervention appears to be a safe and effective method to resect endobronchial hamartomas.

Rationale: The optimal therapeutic regimen and duration of treatment for Mycobacterium abscessus lung disease is not well established., Objectives: To assess the efficacy of a standardized combination antibiotic therapy for the treatment of M. abscessus lung disease., Methods: Sixty-five patients (11 males, 55 females, median age 55 yr) with M. abscessus lung disease were treated with clarithromycin, ciprofloxacin, and doxycycline, together with an initial regimen of amikacin and cefoxitin for the first 4 weeks of hospitalization., Measurements and Main Results: Treatment response rates were 83% for symptoms and 74% for high-resolution computed tomography. Sputum conversion and maintenance of negative sputum cultures for more than 12 months was achieved in 38 (58%) patients. These rates were significantly lower in patients whose isolates were resistant to clarithromycin (17%, 2/12) compared with those whose isolates were susceptible or intermediate to clarithromycin (64%, 21/33; P = 0.007). Neutropenia and thrombocytopenia associated with cefoxitin developed in 33 (51%) and 4 (6%) patients, respectively. Drug-induced hepatotoxicity occurred in 10 (15%) patients. Because of these adverse reactions, cefoxitin was discontinued in 39 (60%) patients after treatment for a median of 22 days., Conclusions: Standardized combination antibiotic therapy was moderately effective in treating M. abscessus lung disease. However, frequent adverse reactions and the potential for long-duration hospitalization are important problems that remain to be solved.

The nodular bronchiectatic form of nontuberculous mycobacterial (NTM) lung disease and diffuse panbronchiolits (DPB) show similar clinical and radiographic findings. The present study was performed to clarify the clinicoradiographic similarities as well as the differences between NTM lung disease and DPB. The initial clinicoradiographic features of 78 patients with the nodular bronchiectatic form of NTM lung disease (41 patients with Mycobacterium avium complex infection and 37 patients with Mycobacterium abscessus infection) were compared with those of 35 patients with DPB. Old age, female sex, a history of tuberculosis treatment, and hemoptysis were related to NTM lung disease while exertional dyspnea, coarse crackles, history of sinusitis, obstructive abnormalities in pulmonary function tests, and hypoxemia were related to DPB. The number of lobes involved with bronchiolitis and bronchiectasis on chest computed tomography were more numerous in DPB patients. There is considerable overlap in the clinical and radiographic appearances of the nodular bronchiectatic form of NTM lung disease and DPB, although some clinicoradiographic features differ between two diseases. The correct diagnosis, including aggressive microbiologic evaluation, should be made for the appropriate management of patients presenting with bilateral bronchiectasis and bronchiolitis.

The early differentiation of Mycobacterium tuberculosis from non-tuberculous mycobacteria (NTM) and the identification of NTM species are crucial for the proper management of patients with smear-positive sputum. We evaluated the usefulness of a polymerase chain reaction restriction analysis (PRA) method based on the rpoB gene for identifying NTM species in a study of 121 smear-positive respiratory specimens with presumed NTM. The PRA method amplified mycobacterial DNA in 72 specimens (60%) and differentiated NTM species correctly in 68 (94%). The PRA method could be a useful and rapid method for identifying NTM species in smear-positive respiratory specimens when urgent clinical decisions are required.

Objective: The purpose of our study was to analyze the high-resolution CT findings of the nodular bronchiectatic form of Mycobacterium avium-intracellulare complex (MAC) pulmonary disease and to correlate the extent of high-resolution CT findings with pulmonary function test (PFT) results., Materials and Methods: From January 2005 through December 2005, we identified 47 patients (mean age, 58 +/- 13 years; age range, 24-72 years; male-female ratio, 11:36) with the nodular bronchiectatic form of MAC pulmonary disease who underwent both high-resolution CT and PFTs. High-resolution CT findings were reviewed retrospectively in terms of the presence and extent of bronchiectasis, cellular or inflammatory bronchiolitis (centrilobular small nodules and tree-in-bud signs), cavity, nodule, and other findings. The extent of the abnormalities seen on high-resolution CT was scored by modifying the cystic fibrosis scoring system proposed by Helbich and coworkers. The scores were correlated with PFT results using Spearman's correlation coefficient., Results: On high-resolution CT, the three most frequently observed patterns of parenchymal abnormalities were, in decreasing order of frequency, cellular bronchiolitis (n = 47, 100%), bronchiectasis (n = 46, 98%), and consolidation (n = 27, 57%). The total CT score showed a significant correlation with the residual volume-total lung capacity (RV/TLC) ratio (r = 0.572, p < 0.001), forced expiratory volume in 1 second (FEV(1)) value (r = -0.426, p = 0.003), forced vital capacity (FVC) value (r = -0.360, p = 0.013), peak expiratory flow value (r = -0.352, p = 0.015), and peak expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75%)) (r = -0.289, p = 0.049)., Conclusion: CT scoring of pulmonary abnormalities correlates with measures of functional impairment in patients with MAC pulmonary disease.

This study evaluated the association between the guanine-thymine (GT) repeat polymorphism in intron II of the Toll-like receptor 2 (TLR2) gene and lung disease caused by nontuberculous mycobacteria (NTM). Polymerase chain reaction and gene scans were used to determine the numbers of GT repeats for 193 patients with the nodular bronchiectatic form of NTM lung disease, including 110 patients with Mycobacterium avium-intracellulare (MAC) infection, 82 patients with Mycobacterium abscessus infection, and 1 patient with co-infection of both organisms. These values were compared with the results for 191 controls. Genotypes with shorter GT repeats were more common among patients with NTM lung disease (50.8 vs 37.7%, p=0.01). In the subgroup analysis, genotypes that included S alleles were more common in the patients with MAC lung disease (53.6%, p=0.01, OR, 1.91; 95% CI, 1.16, 3.16) than in healthy controls, whereas this difference was not statistically significant in patients with M. abscessus lung disease (47.6%, p=0.13). In conclusion, these results suggest that the GT repeat microsatellite polymorphisms in intron II of the human TLR2 gene contribute to the development of NTM lung disease, especially MAC lung disease, in a Korean population.

The pathway involving interferon-gamma and interleukin (IL)-12 plays an important role in host defense against mycobacterial infections. Recent studies have indicated that IL-12 receptor beta1 (IL-12Rbeta1) gene polymorphisms are associated with susceptibility to pulmonary tuberculosis. However, there have been no reports of an association between IL-12Rbeta1 gene polymorphism and lung disease caused by nontuberculous mycobacteria (NTM). The present study involved 128 patients with the nodular bronchiectatic form of NTM lung disease (75 patients with Mycobacterium avium-intracellulare complex infection and 53 patients with Mycobacterium abscessus infection) and 240 healthy controls. Single nucleotide polymorphisms of the IL-12Rbeta1 gene at positions +705A/G, +1158T/C, and +1196G/C were determined by direct sequencing of polymerase chain reaction products. Comparisons of the NTM lung disease patients with healthy controls did not identify any significant differences in relation to the genotype, allele, and haplotype frequencies of the IL-12Rbeta1 +705A/G, +1158T/C, and +1196G/C polymorphisms. These IL-12Rbeta1 gene polymorphisms do not appear to be responsible for host susceptibility to NTM lung disease, at least in this Korean population.

This study investigated the potential role of vitamin D-receptor (VDR) gene polymorphisms in susceptibility to lung disease caused by non-tuberculous mycobacteria (NTM). TaqI and FokI polymorphisms were compared in 124 patients and 127 controls. The genotype, allele and haplotype frequencies did not differ between patients and controls. TaqI and FokI polymorphisms of the VDR gene do not appear to be responsible for host susceptibility to NTM lung disease, at least in this Korean population. An association cannot, however, be completely ruled out, as only two single nucleotide polymorphisms of the VDR gene were studied in this report.

Mycobacterium xenopi is a nontuberculous mycobacterium (NTM) that rarely causes pulmonary disease in Asia. Here we describe the first case of M. xenopi pulmonary disease in Korea. A 66-year-old man was admitted to our hospital with a 2-month history of productive cough and hemoptysis. His past medical history included pulmonary tuberculosis 44 years earlier, leading to a right upper lobectomy. Chest X-ray upon admission revealed cavitary consolidation involving the entire right lung. Numerous acid-fast bacilli were seen in his initial sputum, and M. xenopi was subsequently identified in more than five sputum cultures, using molecular methods. Despite treatment with clarithromycin, rifampicin, ethambutol, and streptomycin, the infiltrative shadow revealed on chest X-ray increased in size. The patient's condition worsened, and a right completion pneumonectomy was performed. The patient consequently died of respiratory failure on postoperative day 47, secondary to the development of a late bronchopleural fistula. This case serves as a reminder to clinicians that the incidence of NTM infection is increasing in Korea and that unusual NTM are capable of causing disease in non-immunocompromised patients.

The aims of the present study were to investigate the expression of Toll-like receptor (TLR)2 on the peripheral blood monocytes of patients with nontuberculous mycobacterial (NTM) lung disease and healthy controls, and to assess the responses of these monocytes to TLR2 agonists such as Mycobacterium avium and lipoteichoic acid (LTA). Reverse transcriptase-PCR was used to analyse TLR2 mRNA expression in peripheral blood monocytes from 17 NTM patients and 10 healthy controls. mRNA and protein secretion levels were also determined for the cytokines interleukin (IL)-12 p40 and tumour necrosis factor (TNF)-alpha. Expression of TLR2 mRNA by peripheral blood monocytes after stimulation with M. avium or LTA was lower in NTM patients than in healthy controls. IL-12 p40 and TNF-alpha mRNA and cytokine secretion levels were also lower in patients than in healthy controls. Treatment with anti-TLR antibody decreased M. avium- and LTA-induced IL-12 p40 and TNF-alpha production in healthy controls, but not in NTM patients. The present results suggest that the downregulation of Toll-like receptor 2 and the resulting decreased production of interleukin-12 p40 and tumour necrosis factor-alpha following Mycobacterium avium or lipoteichoic acid stimulation may contribute to host susceptibility to nontuberculous mycobacterial lung disease.

Interferon-gamma (IFN-gamma) is crucial for host defense against mycobacterial infections. Recent studies have indicated that IFN-gamma and IFN-gamma receptor 1 (IFN-gammaR1) gene polymorphisms are associated with susceptibility to pulmonary tuberculosis. The aim of this study was to test the hypothesis that IFN-gamma and IFN-gammaR1 gene polymorphisms influence susceptibility to lung disease caused by non-tuberculous mycobacteria (NTM). Seventy-six patients with the nodular bronchiectatic form of NTM lung disease (37 patients with Mycobacterium avium complex infection and 39 patients with Mycobacterium abscessus infection) and 80 controls were included. Polymorphisms of the IFN-gamma gene at position +874 were determined by the amplification refractory mutation system (ARMS) polymerase chain reaction assay and IFN-gammaR1 gene at positions -611, -270, -56 and +95 was genotyped by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry using genomic DNA. IFN-gammaR1 -270 and +95 polymorphisms were not present in any of the patients or controls. The patients with NTM lung disease showed no significant difference from controls in genotype and allele frequencies of the IFN-gamma +874 and IFN-gammaR1 -611 and -56 polymorphisms. The IFN-gamma +874 and IFN-gammaR1 -611 and -56 polymorphisms do not appear to be responsible for host susceptibility to NTM lung disease, at least in the Korean population.

Objective: To compare the clinical and radiographic features of pulmonary tuberculosis (PTB) and non-tuberculous mycobacteria (NTM) lung disease in patients with acid-fast bacilli (AFB) positive sputum specimens., Design: The initial clinical and radiographic features of 229 PTB patients were compared with those of 70 patients with NTM lung disease. The most commonly involved organisms in the NTM lung disease cases were Mycobacterium avium complex (n = 38, 54%) and M. abscessus (n = 26, 37%)., Results: Clinical and radiographic findings that were more common in patients with NTM lung disease than in PTB patients were: older age (P < 0.001), non-smoker (P < 0.001), history of previous TB treatment (P < 0.001), absence of pleural effusion (P = 0.017), involvement of middle and/or lower lung zones (P = 0.007), and bilateral disease (P = 0.005). Multivariate analysis showed that older age (> or = 40 years), non-smoker, previous TB treatment, absence of pleural effusion and involvement of middle and/or lower lung zones were significant independent predictors for NTM lung disease., Conclusions: There is considerable overlap in the clinical and radiographic appearances of PTB and NTM lung disease. The isolation and identification of causative organisms are mandatory for a correct diagnosis in patients with AFB-positive sputum specimens.

Interferon-gamma (IFN-gamma) plays a key role in the host defense response against mycobacterial disease, and a complete or partial deficiency in IFN-gamma receptor 1 (IFN-gammaR1) or IFN-gamma receptor 2 (IFN-gammaR2) has been reported to contribute to susceptibility to disseminated infection with non-tuberculous mycobacteria (NTM). However, IFN-gammaR1 and IFN-gammaR2 deficiencies have not yet been studied in adult patients with isolated NTM lung disease. The purpose of the present study was to evaluate whether partial IFN-gammaR1 and IFN-gammaR2 deficiency are associated with human susceptibility to NTM lung disease. We studied 40 patients with NTM lung disease (Mycobacterium avium complex infection, 20 patients; Mycobacterium abscessus infection, 20 patients) for partial IFN-gammaR1 and IFN-gammaR2 deficiency. Genomic DNA was amplified by polymerase chain reaction and sequenced for revealing mutations of the IFN-gammaR1 and IFN-gammaR2 gene. None of the patients had previously reported homozygous recessive missense mutation causing an amino-acid substitution in the extracellular domain of the receptor (I87T) and hotspot for small deletions (818delT, 818del4) of the IFN-gammaR1 or homozygous missense mutation (R114C) of the IFN-gammaR2. In conclusion, in adult patients with isolated NTM lung disease, there is no evidence for previously known genetic defects of partial deficiencies of IFN-gammaR1 and IFN-gammaR2 to correlate with disease.

To investigate the occurrence of the Toll-like receptor 2 (TLR2) polymorphisms in patients with pulmonary disease caused by nontuberculous mycobacteria (NTM), TLR2 Arg677Trp and Arg753Gln polymorphisms were examined. TLR2 polymorphisms do not appear to be responsible for host susceptibility to NTM lung disease, at least in the Korean population.

The incidence of pulmonary disease caused by nontuberculous mycobacteria (NTM) appears to be increasing worldwide. In Korea, M. avium complex and M. abscessus account for most of the pathogens encountered, whilst M. kansasii is a relatively uncommon cause of NTM pulmonary diseases. NTM pulmonary disease is highly complex in terms of its clinical presentation and management. Because its clinical features are indistinguishable from those of pulmonary tuberculosis and NTMs are ubiquitous in the environment, the isolation and identification of causative organisms are mandatory for diagnosis, and some specific diagnostic criteria have been proposed. The treatment of NTM pulmonary disease depends on the infecting species, but decisions concerning the institution of treatment are never easy. Treatment requires the use of multiple drugs for 18 to 24 months. Thus, treatment is expensive, often has significant side effects, and is frequently not curative. Therefore, clinicians should be confident that there is sufficient pathology to warrant prolonged, multidrug treatment regimens. In all of the situations, outcomes can be best optimized only when clinicians, radiologists, and laboratories work cooperatively.

We aimed to compare the CT findings of nontuberculous mycobacterial pulmonary diseases caused by Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus. Two chest radiologists analyzed retrospectively the thin-section CT findings of 51 patients with MAC and 36 with M. abscessus infection in terms of patterns and forms of lung lesions. No significant difference was found between MAC and M. abscessus infection in the presence of small nodules, tree-in-bud pattern, and bronchiectasis. However, lobar volume decrease (p=0.001), nodule (p=0.018), airspace consolidation (p=0.047) and thin-walled cavity (p=0.009) were more frequently observed in MAC infection. The upper lobe cavitary form was more frequent in the MAC (19 of 51 patients, 37%) group than M. abscessus (5 of 36, 14%) (p=0.029), whereas the nodular bronchiectatic form was more frequent in the M. abscessus group ([29 of 36, 81%] vs. [27 of 51, 53%] in MAC) (p=0.012). In conclusion, there is considerable overlap in common CT findings of MAC and M. abscessus pulmonary infection; however, lobar volume loss, nodule, airspace consolidation, and thin-walled cavity are more frequently seen in MAC than M. abscessus infection.

Study Objective: Paragonimiasis is a typical food-borne parasitic disease that is common in Southeast Asia, the Far East, Latin American, and Africa. Recently, however, this disease has been seen in many parts of the world, largely due to increases in the numbers of immigrants and overseas travelers. The purpose of this study was to evaluate the clinical and radiologic features of recently diagnosed pulmonary paragonimiasis., Patients: We retrospectively analyzed the clinical and radiologic characteristics of 36 patients (21 men and 15 women; median age 48 years; range, 19 to 75) with pulmonary paragonimiasis whose conditions were diagnosed between October 1994 and September 2004., Results: Thirty-four patients (94%) presented with respiratory symptoms, including hemoptysis (n = 20, 56%) and cough (n = 17, 47%). However, chest pain (n = 5, 14%) and fever (n = 5, 14%) were less frequently reported. Chest radiography revealed intrapulmonary parenchymal lesions (n = 26, 72%), such as nodules (n = 14, 39%), linear opacity (n = 6, 17%), and airspace consolidations (n = 4, 11%), which occurred more commonly than did pleural lesions (n = 10, 28%). Most cases were initially suspected to be lung cancer or tuberculosis. In 13 patients with intrapulmonary parenchymal lesions who underwent bronchoscopy, bronchial luminal narrowing, coupled with congested or edematous mucosal changes, was seen in 7 patients (54%). Bronchial mucosal biopsy specimens exhibited chronic inflammation with eosinophilic infiltrations in three of these seven patients (43%)., Conclusions: Our findings indicate that patients with pulmonary paragonimiasis presented with a variety of clinical and radiologic findings that were different from the classic presentations reported earlier, frequently mimicking those of lung cancer or tuberculosis.

Study Objectives: Pulmonary disease caused by nontuberculous mycobacteria (NTM) may occur in patients with no underlying lung disease and no known immunodeficiency. The purpose of this study was to evaluate a potential role for natural-resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms for human susceptibility to the NTM lung disease., Design: A case-control study., Setting: Tertiary university medical center., Participants: Forty-one adult patients with NTM lung disease (Mycobacterium avium complex infection, 18 patients; Mycobacterium abscessus infection, 23 patients) were included in the study population. The diagnosis of NTM lung disease was made when the patients fulfilled the diagnostic criteria published by the American Thoracic Society. All patients had findings on high-resolution CT scans, such as bilateral bronchiectasis combined with multiple small nodules and branching linear structures, that were characteristic of the nodular bronchiectatic form of NTM lung disease. Fifty healthy individuals were selected as control subjects., Results: Heterozygotes at intron 4 (469 + 14G/C) [INT4], codon 543 in exon 15 (D543N), and 3' untranslated region (3'UTR) were observed at significantly higher frequencies in patients with NTM lung disease than in control subjects. The odds ratios (ORs) were 2.78 (95% confidence interval [CI], 1.12 to 6.89; p = 0.026) for INT4 G/C, 5.74 (95% CI, 1.48 to 22.30; p = 0.006) for D543 G/A, and 9.54 (95% CI, 2.49 to 36.53; p < 0.001) for 3'UTR TGTG+/del. Subjects who were heterozygous for two NRAMP1 polymorphisms in INT4 and D543N were particularly overrepresented among those with NTM lung disease, compared with those with the most common NRAMP1 genotype (OR, 10.88, 95% CI, 1.18 to 100.45; p = 0.035). There were no significant differences in the frequencies of INT4, D543N, and 3'UTR polymorphisms between the patients with M avium complex infection and those with M abscessus infection., Conclusions: These findings suggest that the NRAMP1 genetic polymorphisms are associated with human susceptibility to NTM lung disease.

Metabolic lung disease includes pulmonary alveolar proteinosis (PAP), pulmonary amyloidosis, metastatic pulmonary calcification, dendritic pulmonary ossification, pulmonary alveolar microlithiasis, and storage diseases. In pulmonary alveolar proteinosis, CT demonstrates air-space consolidation with thickened interlobular septa, producing the so-called "crazy paving" appearance. Pulmonary amyloidosis can appear as parenchymal nodules (nodular parenchymal form), diffuse interstitial deposit (diffuse interstitial form), or submucosal deposits in the airways (tracheobronchial form). Metastatic pulmonary calcification may appear on high-resolution CT as numerous 3- to 10-mm diameter calcified nodules or, more commonly as fluffy and poorly defined nodular opacities. In pulmonary microlithiasis, high-resolution CT demonstrates diffuse punctuate micronodules showing slight perilobular predominance resulting in apparent calcification of interlobular septa. Niemann-Pick disease appears as ground-glass attenuation in the upper lung zone and thickening of the interlobular septa in the lower lung zone. Radiologic study including high-resolution CT will be helpful for the diagnosis and follow-up of these diseases.

Objective: The objectives of our study were to evaluate the thin-section CT findings of the cavitary form of nontuberculous mycobacterial pulmonary infection and correlate these imaging findings with the histopathologic findings concerning the development of bronchiectasis and of centrilobular nodules and cavitary lesions., Materials and Methods: We retrospectively reviewed thin-section CT scans (2.5-mm collimation, both axial and coronal reformation images) of 24 cases (male-female ratio, 13:11; mean age, 61 years; age range, 43-82 years) of the cavitary form of culture-proven Mycobacterium avium-intracellulare complex pulmonary infection including two cases with lobectomy specimens. Any changes in CT findings detected on the follow-up CT scans that were available for seven patients (follow-up interval, 6-24 months; mean, 12 months) were also assessed., Results: Thin-section CT findings were bronchiectasis (24/24 patients, 100%), a patent bronchus running into a cavitary lesion (the "feeding bronchus" appearance) (18/24, 75%), nodules less than 10 mm (17/24, 71%), centrilobular nodules (17/24, 71%), nodules of 10-30 mm (13/24, 54%), peribronchial nodules (8/24, 33%), lobular consolidation (6/24, 25%), bronchial wall thickening (4/24, 17%), and consolidation (2/24, 8%). Two lobectomy specimens showed large cavitary consolidations with the feeding bronchus appearance on pathologic specimens. In two patients, small peribronchial nodules had changed into cavitary nodules with the feeding bronchus appearance on follow-up CT, which represented inflamed focal cystic bronchiectasis., Conclusion: In the cavitary form of M. avium-intracellulare complex pulmonary infection, the feeding bronchus appearance is another very frequent thin-section CT finding. This appearance may suggest that peribronchial nodules of M. avium-intracellulare complex infection evolve into inflamed focal cystic bronchiectasis manifesting as cavitary lesions.

The radiological manifestations of pulmonary nocardiosis are very diverse, and include non-segmental consolidation and pulmonary nodule(s). Cavitary nodules most commonly appear in AIDS patients, and are uncommon in non-AIDS patients. We report a case of pulmonary nocardiosis with bilateral multiple cavitary nodules in a HIV-negative 60-year-old man with nephrotic syndrome who was receiving corticosteroid treatment. It is suggested that pulmonary nocardiosis should be considered in the differential diagnosis of multiple cavitary nodules on chest radiographs, even in non-AIDS immunocompromised patients.